Variability of PD-L1 expression in mastocytosis

Ellen W. Hatch, Mary Beth Geeze, Cheyenne Martin, Mohamed Salama, Karin Hartmann, Gregor Eisenwort, Katharina Blatt, Peter Valent, Jason Gotlib, Ji Hyun Lee, Lu Chen, Heather H. Ward, Diane S. Lidke, Tracy I. George

Research output: Contribution to journalArticle

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Abstract

Mastocytosis is a rare disease with heterogeneous clinical manifestations and few effective therapies. Programmed death-1 (PD-1) and its ligands (PD-L1 and PD-L2) protect tissues from immune-mediated damage and permit tumors to evade immune destruction. Therapeutic antibodies against PD-1 and PD-L1 are effective in the treatment of a variety of neoplasms. In the present study, we sought to systematically analyze expression of PD-1 and PD-L1 in a large number of patients with mastocytosis using immunohistochemistry and multiplex fluorescence staining. PD-L1 showed membrane staining of neoplastic mast cells (MCs) in 77% of systemic mastocytosis (SM) cases including 3 of 3 patients with MC leukemia, 2 of 2 with aggressive SM, 1 of 2 with smoldering SM, 3 of 4 with indolent SM, and 9 of 12 with SM with an associated hematologic neoplasm (SM component only). Ninety-two percent (23 of 25) of cutaneous mastocytosis (CM) cases and 1 of 2 with myelomastocytic leukemia expressed PD-L1, with no expression found in 15 healthy/reactive marrows, 18 myelodysplastic syndromes (MDSs), 16 myeloproliferative neoplasms (MPNs), 5 MDS/MPNs, and 3 monoclonal MC activation syndromes. Variable PD-L1 expression was observed between and within samples, with PD-L1 staining of MCs ranging from 10% to 100% (mean, 50%). PD-1 dimly stained 4 of 27 CM cases (15%), with no expression in SM or other neoplasms tested; PD-1 staining of MCs ranged from 20% to 50% (mean, 27%). These results provide support for the expression of PD-L1 in SM and CM, and PD-1 expression in CM. These data support the exploration of agents with anti-PD-L1 activity in patients with advanced mastocytosis.

Original languageEnglish (US)
Pages (from-to)189-199
Number of pages11
JournalBlood Advances
Volume2
Issue number3
DOIs
StatePublished - Feb 13 2018
Externally publishedYes

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Systemic Mastocytosis
Mastocytosis
Cutaneous Mastocytosis
Mast Cells
Staining and Labeling
Myelodysplastic Syndromes
Neoplasms
Mast-Cell Leukemia
Hematologic Neoplasms
Rare Diseases
Leukemia
Therapeutics
Fluorescence
Bone Marrow
Immunohistochemistry
Ligands
Membranes
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hatch, E. W., Geeze, M. B., Martin, C., Salama, M., Hartmann, K., Eisenwort, G., ... George, T. I. (2018). Variability of PD-L1 expression in mastocytosis. Blood Advances, 2(3), 189-199. https://doi.org/10.1182/bloodadvances.2017011551

Variability of PD-L1 expression in mastocytosis. / Hatch, Ellen W.; Geeze, Mary Beth; Martin, Cheyenne; Salama, Mohamed; Hartmann, Karin; Eisenwort, Gregor; Blatt, Katharina; Valent, Peter; Gotlib, Jason; Lee, Ji Hyun; Chen, Lu; Ward, Heather H.; Lidke, Diane S.; George, Tracy I.

In: Blood Advances, Vol. 2, No. 3, 13.02.2018, p. 189-199.

Research output: Contribution to journalArticle

Hatch, EW, Geeze, MB, Martin, C, Salama, M, Hartmann, K, Eisenwort, G, Blatt, K, Valent, P, Gotlib, J, Lee, JH, Chen, L, Ward, HH, Lidke, DS & George, TI 2018, 'Variability of PD-L1 expression in mastocytosis', Blood Advances, vol. 2, no. 3, pp. 189-199. https://doi.org/10.1182/bloodadvances.2017011551
Hatch EW, Geeze MB, Martin C, Salama M, Hartmann K, Eisenwort G et al. Variability of PD-L1 expression in mastocytosis. Blood Advances. 2018 Feb 13;2(3):189-199. https://doi.org/10.1182/bloodadvances.2017011551
Hatch, Ellen W. ; Geeze, Mary Beth ; Martin, Cheyenne ; Salama, Mohamed ; Hartmann, Karin ; Eisenwort, Gregor ; Blatt, Katharina ; Valent, Peter ; Gotlib, Jason ; Lee, Ji Hyun ; Chen, Lu ; Ward, Heather H. ; Lidke, Diane S. ; George, Tracy I. / Variability of PD-L1 expression in mastocytosis. In: Blood Advances. 2018 ; Vol. 2, No. 3. pp. 189-199.
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